Tiotropium bromide (compound identified by CAS registry number 136310-93-5) was described for the first time in 1991 by Boheringer Inghelheim (EP 0418716) and presents the following structural formula:

Tiotropium bromide is an anticholinergic bronchodilator with a long-lasting effect, 24 hours, which may be used to treat respiratory complaints, particularly COPD (chronic obstructive pulmonary disease), bronchitis, emphysema and asthma.
Tiotropium bromide is preferably administered by inhalation: suitable inhalable powders packed into appropriate capsules may be used (Spiriva®; U.S. Pat. Nos. 7,694,676 and 8,022,082) or alternatively, it may be administered by the use of inhalable aerosols (EP2201934).
The correct manufacture of the above mentioned compositions, suitable for the administration of a pharmaceutically active substance by inhalation, is based on the definition of physical parameters, like a particular crystalline form (see for example U.S. Pat. Nos. 6,608,055 and 677,423) and a defined particle size distribution (U.S. Pat. No. 7,070,800), which are connected with the nature of the active substance itself.
From literature data, Tiotropium Bromide is described to exist in different polymorphic forms as well as in an amorphous form. In more details, Tiotropium Bromide is described to exist in a crystalline monohydrate form (U.S. Pat. No. 6,777,423), in several anhydrous (U.S. Pat. No. 6,608,055, WO2006/117300, EP1682542) and solvate (U.S. Pat. No. 7,879,871, WO2010/101538, WO2011/015882) polymorphic forms. Some of these polymorphic forms are unstable and may change. For example, the monohydrate form described in U.S. Pat. No. 6,777,423 may be easily transformed after a mild heating at 40° C. for few hours into the corresponding anhydrous form described in U.S. Pat. No. 6,608,055.
Since the quality of a pharmaceutical formulation requires that an active substance should always have the same crystalline modification, the stability and properties of the crystalline active substance are subject to stringent regulatory requirements.
There is the need of a crystalline form of tiotropium bromide which is stable to humidity and to mechanical treatments, like the micronization or other milling techniques, and which meets the high demands mentioned above for any pharmaceutically active substance.